Does the angle of trocar insertion affect the fascial defect caused? A porcine model.

INTRODUCTION: With an incidence of 0-5.2%, trocar site hernias frequently occur following laparoscopy. It is unclear to what extent the angle of trocar insertion affects the size of the fascial defect caused. Hence, we performed a porcine model. METHODS: In October 2022, a total of five female pigs were euthanized. In alternating order, three bladeless and two bladed conical 12-mm trocars were inserted at an angle of 45° on each side for 60 min twice each pig. For this purpose, an epoxy resin handmade cuboid with a central channel that runs at an angle of 45° was used. Subsequently, photo imaging and defect size measurement took place. The results were compared with those of our previously conducted and published porcine model, in which the trocars were inserted at an angle of 90°. Effects of trocar type (bladed vs. bladeless) and angle on defect size were analyzed using a mixed model regression analysis. RESULTS: The bladeless trocars caused statistically significant smaller defects at the fascia than the bladed (23.4 (SD = 16.9) mm2 vs. 41.3 (SD = 14.8) mm2, p < 0.001). The bladeless VersaOne trocar caused the smallest defect of 16.0 (SD = 6.1) mm2. The bladed VersaOne trocar caused the largest defect of 47.7 (SD = 10.5) mm2. The defect size of the trocars used at a 45° angle averaged 30.5 (SD = 18.3) mm2. The defect size of trocars used at a 90° angle was significantly larger, averaging 58.3 (SD = 20.2) mm2 (p = 0.007). CONCLUSION: When conical 12-mm trocars are inserted at a 45° angle, especially bladeless ones, they appear to cause small fascial defects compared with insertion at a 90° angle. This might lead also to a lower rate of trocar hernias. Bladeless trocars might cause smaller fascial defects than bladed trocars.

Complete mesocolic excision for right hemicolectomy: an updated systematic review and meta-analysis.

PURPOSE: Complete mesocolic excision improves lymphadenectomy for right hemicolectomy and respects the embryological planes. However, its effect on cancer-free and overall survival is questioned. Therefore, we aimed to determine the potential benefits of the technique by performing a systematic review of the literature and meta-analysis of the available evidence. METHODS: Web of Science, PubMed/Medline, and Embase were searched on February 22, 2023. Original studies on short- and long-term oncological outcomes of adult patients undergoing right hemicolectomy with complete mesocolic excision as a treatment for primary colon cancer were considered for inclusion. Outcomes were extracted and pooled using a model with random effects. RESULTS: A total of 586 publications were identified through database searching, and 18 from citation searching. Exclusion of 552 articles left 24 articles for inclusion. Meta-analysis showed that complete mesocolic excision increased the lymph node harvest (5 studies, 1479 patients, MD 9.62, 95% CI 5.83-13.41, p > 0.0001, I2 84%), 5-year overall survival (5 studies, 2381 patients, OR 1.88, 95% CI 1.14-3.09, p = 0.01, I2 66%), 5-year disease-free survival (4 studies, 1376 patients, OR 2.21, 95% CI 1.51-3.23, p < 0.0001, I2 0%) and decreased the incidence of local recurrence (4 studies, 818 patients, OR 0.27, 95% CI 0.09-0.79, p = 0.02, I2 0%) when compared to standard right hemicolectomy. Perioperative morbidity was similar between the techniques (8 studies, 3899 patients, OR 1.04, 95% CI 0.89-1.22, p = 0.97, I2 0%). CONCLUSION: Meta-analysis of observational and randomised studies showed that right hemicolectomy with complete mesocolic excision for primary right colon cancer improves oncologic results without increasing morbidity/mortality. These results need to be confirmed by high-quality evidence and randomised trials in selected patients to assess who may benefit from the procedure.

Transcriptional and Epigenetic Regulation of Context-Dependent Plasticity in T-Helper Lineages.

Th cell lineage determination and functional specialization are tightly linked to the activation of lineage-determining transcription factors (TFs) that bind cis-regulatory elements. These lineage-determining TFs act in concert with multiple layers of transcriptional regulators to alter the epigenetic landscape, including DNA methylation, histone modification and three-dimensional chromosome architecture, in order to facilitate the specific Th gene expression programs that allow for phenotypic diversification. Accumulating evidence indicates that Th cell differentiation is not as rigid as classically held; rather, extensive phenotypic plasticity is an inherent feature of T cell lineages. Recent studies have begun to uncover the epigenetic programs that mechanistically govern T cell subset specification and immunological memory. Advances in next generation sequencing technologies have allowed global transcriptomic and epigenomic interrogation of CD4+ Th cells that extends previous findings focusing on individual loci. In this review, we provide an overview of recent genome-wide insights into the transcriptional and epigenetic regulation of CD4+ T cell-mediated adaptive immunity and discuss the implications for disease as well as immunotherapies.

Dynamics of Viral and Host 3D Genome Structure upon Infection.

Eukaryotic chromatin is highly organized in the 3D nuclear space and dynamically regulated in response to environmental stimuli. This genomic organization is arranged in a hierarchical fashion to support various cellular functions, including transcriptional regulation of gene expression. Like other host cellular mechanisms, viral pathogens utilize and modulate host chromatin architecture and its regulatory machinery to control features of their life cycle, such as lytic versus latent status. Combined with previous research focusing on individual loci, recent global genomic studies employing conformational assays coupled with high-throughput sequencing technology have informed models for host and, in some cases, viral 3D chromosomal structure re-organization during infection and the contribution of these alterations to virus-mediated diseases. Here, we review recent discoveries and progress in host and viral chromatin structural dynamics during infection, focusing on a subset of DNA (human herpesviruses and HPV) as well as RNA (HIV, influenza virus and SARS-CoV-2) viruses. An understanding of how host and viral genomic structure affect gene expression in both contexts and ultimately viral pathogenesis can facilitate the development of novel therapeutic strategies.

Intercalary and geographic lower limb tumor resections with the use of 3D printed Patient Specific Instruments- when less is more.

Background: Primary bone sarcomas are associated with critically sized bone defects and require complete resection with negative margins. Recent advancements in health care have pioneered novel approaches such as the implementation of 3D surgical technologies. This study presents oncological and functional outcomes following tumor resections of long bones with the use of customized 3D-printed Patient Specific Instruments (PSIs). Methods: This single-center retrospective study is comprised of seventeen patients who underwent either intercalary (N = 12) or geographic (N = 5) resections with various reconstruction methods including allograft (N = 8), vascularized fibula (Capanna) (N = 7), and 3D printed customized titanium implants (N = 2), between the years 2016-2020. All patients were operated on with a 3D surgical workflow, including intraoperative PSIs, and were followed up postoperatively for at least 12 months (average 31.40 ± 12.13 months) to assess oncological and functional outcomes. Results: All patients demonstrated negative surgical margins, apart from one patient who had planned positive margins. Three patients suffered from short-term complications, and three patients underwent revision surgery due to graft non-union or pathological fracture. One patient suffered from local recurrence and underwent above-knee amputation. Three patients suffered from lung metastasis. MSTS at 12-month follow-up was 26.9.±5.87. Conclusion: Customized 3D-printed osteotomy PSIs provide surgeons with a novel tool for optimizing bone resection and reconstruction in long bones surgeries, thus minimizing overall tissue trauma and reducing the risk of damage to nervous and vascular structures. This study demonstrates that the use of PSIs has the potential to improve functional and oncological outcomes. We believe that this technique will become increasingly popular in the future as a widely applicable, highly accurate, cost-effective optimization tool.

Efficacy and Safety of Reirradiation with Stereotactic Body Radiation Therapy for Locally Recurrent Pancreatic Adenocarcinoma.

AIMS: The purpose of this study was to report on outcomes of a cohort of patients who were treated with reirradiation with stereotactic body radiation therapy (SBRT) for locally recurrent pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients treated with SBRT reirradiation for locally recurrent pancreatic adenocarcinoma from December 2009 to April 2020 were included in the study. Descriptive statistics were used to record patient demographics, tumour and treatment characteristics. Kaplan-Meier analysis was used to evaluate overall survival, local progression-free survival (LPFS), distant metastasis-free survival and progression-free survival (PFS). RESULTS: In total, 27 patients were included in the study. The median follow-up time from local recurrence was 19.7 months (range 4.2-43.1 months). Most patients received five-fraction SBRT (26/27, 96%). The median overall survival after local recurrence treatment was 18.3 months (range 3.0-42.6 months), with 6-month, 1-year and 2-year overall survival rates of 88.5%, 73.1% and 33.6%. The median LPFS after local recurrence treatment was 16.2 months (range 2.3-33.6 months), with 6-month, 1-year and 2-year LPFS rates of 95.8%, 62.9% and 27.2%. Peri-SBRT chemotherapy improved LPFS (median 17.5 versus 8.5 months; P = 0.010) and overall survival (median 19.3 versus 5.5 months; P = 0.049). Tumours ≤ 3 cm in the greatest dimension showed better local control (median LPFS 19.2 versus 10.2 months; P = 0.130). There was one case (4%) of acute grade 3 pain and one case (4%) of late grade 3 gastrointestinal toxicity. CONCLUSIONS: Reirradiation with five-fraction SBRT is safe, but local control remains suboptimal. Patients with smaller tumours experienced improved outcomes, as did patients whose treatment plan included the administration of peri-SBRT chemotherapy.

A systematic review and meta-analysis of robotic-assisted transabdominal total mesorectal excision and transanal total mesorectal excision: which approach offers optimal short-term outcomes for mid-to-low rectal adenocarcinoma?

BACKGROUND: Resection of low rectal adenocarcinoma can be challenging in the narrow pelvis of male patients. Transanal total mesorectal excision (TaTME) appears to offer technical advantages for distal rectal tumours, and robotic-assisted transabdominal TME (rTME) was introduced in effort to improve operative precision and ergonomics. However, no study has comprehensively compared these approaches. The aim of the present study was to perform a systematic review of the literature to compare postoperative short-term outcomes in rTME and TaTME. METHODS: A systematic online search (1974-July 2020) of MEDLINE, Embase, web of science and google scholar was conducted for trials, prospective or retrospective studies involving rTME, or TaTME for rectal cancer. Outcome variables included: hospital stay; operation duration, blood loss; resection margins; proportion of histologically complete resected specimens; lymph nodes; overall complications; anastomotic leak, and 30-day mortality. RESULTS: Sixty-two articles met the inclusion criteria, including 37 studies (3835 patients) assessing rTME resection, 23 studies (1326 patients) involving TaTME and 2 comparing both (165 patients). Operating time was longer in rTME (309.2 min, 95% CI 285.5-332.8) than in TaTME studies (256.2 min, 95% CI 231.5-280.9) (p = 0.002). rTME resected specimens had a larger distal resection margin (2.62 cm, 95% CI 2.35-2.88) than in TaTME studies (2.10 cm, 95% CI 1.83-2.36) (p = 0.007). Other outcome variables did not significantly differ between the two techniques. CONCLUSIONS: rTME provides similar pathological and short-term outcomes to TaTME and both are reasonable surgical approaches for patients with mid-to-low rectal cancer. To definitively answer the question of the optimal TME technique, we suggest a prospective trial comparing both techniques assessing long-term survival as a primary outcome.

Non-dissecting large thoracic aortic aneurysm leading to chronic aortic insufficiency presenting as acute heart failure.

Large, non-dissecting thoracic aortic aneurysms (TAA) up to 13 cm in size are typically found in elderly patients with non-specific respiratory symptoms yet must be detected quickly due to their mortality risk. We present a 31-year-old man with exertional dyspnea secondary to aortic insufficiency from a 9.4 cm TAA.

Tools for optimising pharmacotherapy in psychiatry (therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests): focus on antidepressants.

Objectives: More than 40 drugs are available to treat affective disorders. Individual selection of the optimal drug and dose is required to attain the highest possible efficacy and acceptable tolerability for every patient.Methods: This review, which includes more than 500 articles selected by 30 experts, combines relevant knowledge on studies investigating the pharmacokinetics, pharmacodynamics and pharmacogenetics of 33 antidepressant drugs and of 4 drugs approved for augmentation in cases of insufficient response to antidepressant monotherapy. Such studies typically measure drug concentrations in blood (i.e. therapeutic drug monitoring) and genotype relevant genetic polymorphisms of enzymes, transporters or receptors involved in drug metabolism or mechanism of action. Imaging studies, primarily positron emission tomography that relates drug concentrations in blood and radioligand binding, are considered to quantify target structure occupancy by the antidepressant drugs in vivo. Results: Evidence is given that in vivo imaging, therapeutic drug monitoring and genotyping and/or phenotyping of drug metabolising enzymes should be an integral part in the development of any new antidepressant drug.Conclusions: To guide antidepressant drug therapy in everyday practice, there are multiple indications such as uncertain adherence, polypharmacy, nonresponse and/or adverse reactions under therapeutically recommended doses, where therapeutic drug monitoring and cytochrome P450 genotyping and/or phenotyping should be applied as valid tools of precision medicine.

Levator ani and puborectalis muscle rupture: diagnosis and repair for perineal instability.

BACKGROUND: Puborectalis muscle rupture usually arises from peri-partum perineal trauma and may result in anterior, middle compartment prolapses, posterior compartment prolapse which includes rectocele and rectal prolapse, with or without associated anal sphincter damage. Patients with puborectalis muscle and levator ani rupture may present some form of incontinence or evacuation disorder, sexual dysfunction or pelvic organ descent. However, the literature on this subject is scarce. The aim of our study was to evaluate management and treatment of functional disorders associated with puborectalis and/or pubococcygei rupture at the level of the insertion in the pubis in a cohort of patients referred to a tertiary care coloproctology center. METHODS: We conducted a prospective cohort study of patients with levator ani and puborectalis muscle avulsion in the Proctology and Pelvic Floor Unit, Division of Digestive Surgery of the University Hospitals of Geneva from January 2001 to November 2018. Clinical examination, anoscopy and ultrasound were performed on a routine basis. Rupture of the levator ani muscle was diagnosed by clinical examination and ultrasound. A Wexner incontinence score was completed before and 6 months after surgery. Levator ani muscle repair was performed using a transvaginal approach. RESULTS: Fifty-two female patients (median age 56 ± 11.69 SD years, range 38-86 years) were included in the study. Thirty-one patients (59.6%) had anal incontinence, 25 (48.1%) urinary incontinence, 28 (53.9%) dyschezia (obstructive defecation or excessive straining to defecate), 20 (38.5%) dyspareunia, 17 (32.7%) colpophony, and 13 (25.0%) impaired sensation during sexual intercourse. Deviation of the anus on the side opposite the lesion was observed in 50 patients (96.2%), confirmed with clinical examination and both endoanal and perineal ultrasound. Out of these 52 patients, levator ani rupture (including puborectalis rupture) were categorized into right sided, 43 (82.69%), left sided, 7 (13.46%) and bilateral, 2 (3.85%). Levator ani muscle repair was performed in all patients, associated with posterior repair and levatorplasty in 26 patients (50%) and with sphincteroplasty in 34 patients (63.4%). Four patients (7.7%) experienced postoperative complications: significant postoperative pain (n = 3; 5.77%), urinary retention (n = 2; 3.85%), hematoma (n = 1; 1.92%), and perineal abscess (n = 1; 1.92%). Forty-one patients (78.8%) had full restoration of normal puborectalis muscle function (Wexner score: 0/20) after surgery, and overall, all patients had an improvement in the Wexner score and in sexual function. Dyschezia was reported by 28 patients (53.9%) preoperatively, resolved in 18 (64.3%) and improved by 50% or more in 10 (35.71%). CONCLUSIONS: Diagnosis of levator ani and puborectalis muscle rupture requires careful history taking, clinical examination, endoanal and perineal ultrasound. Surgical repair improved anal continence as well as sexual function in all patients. Transvaginal levator ani repair seems to be well tolerated with good short-term results.

CERKL is upregulated in cutaneous squamous cell carcinoma and maintains cellular sphingolipids and resistance to oxidative stress.

BACKGROUND: Ceramide kinase-like protein (CERKL) was originally described in retinal tissue. CERKL has been shown to protect cells from oxidative stress, and mutations in CERKL underlie the inherited disease retinitis pigmentosa. CERKL expression maintains cellular sphingolipids via an unknown mechanism. OBJECTIVES: To determine whether CERKL is expressed in epidermis and cutaneous squamous cell carcinoma (cSCC) and whether CERKL expression affects cSCC sphingolipid metabolism and susceptibility to oxidative stress. METHODS: CERKL expression was determined by RNA-Seq, quantitative polymerase chain reaction and immunohistochemistry. CERKL was knocked down in cSCC cells using small interfering RNA. Sphingolipid content was analysed by liquid chromatography-mass spectrometry. Oxidative stress was induced by treatment with H2 O2 , and apoptosis was measured using flow cytometry to determine annexin V binding. RESULTS: CERKL mRNA and protein are highly expressed in actinic keratosis and cSCC in comparison with normal epidermis. CERKL is also expressed in metabolically active epithelial cells in normal hair bulbs and sebaceous glands. CERKL knockdown in cultured cSCC cells reduces cellular sphingolipid content and enhances susceptibility to oxidative stress. CONCLUSIONS: These findings suggest that CERKL may be important in cSCC progression and could lead to novel strategies for prevention and treatment of cSCC.

Development and implementation of an assessment tool to evaluate technical skills in the insertion of implantable venous access devices, a Prospective Cohort Study.

OBJECTIVE: Based on the Competency Assessment Tool, herein we developed an assessment instrument suitable to evaluate the implantation of central intravenous devices. BACKGROUND: Surgical assessment is based mainly on the subjective impressions of the teacher. Based on the "Competency Assessment Tool" (CAT) developed for the evaluation of technical surgical skills in minimally invasive colorectal resection, we designed an assessment tool suitable to evaluate the implantation of central venous access devices performed by junior surgical trainees. METHODS: Four major assessments during the different steps of the intervention were used in this evaluation. Each of these tasks was divided into four sub-domains according to surgical skill. In addition to the CAT score, the apprentices' skills were evaluated using a visual assessment that was quantified using an analogue scale (value from 1 to 10). The candidates were classified into junior and senior trainees depending on the number of procedures they had already performed and on their surgical experience. RESULTS: 71 procedures were evaluated during the study period. Seven senior trainees conducted 43 procedures and five junior trainees performed 28 interventions. The senior trainees had significantly higher CAT scores than junior candidates, and the scores fluctuated according to surgical experience, usually reaching their peak after 10 procedures. CONCLUSIONS: The CAT model is well suited for the assessment of surgical trainees during central venous access device implantation. It enables a close assessment of the learning process and the technical skills of trainees, which helps them improving in a safe, standardized manner.

Measurement of airway pressure during high-flow nasal therapy in apnoeic oxygenation: a randomised controlled crossover trial.

It is recognised that high-flow nasal therapy can prevent desaturation during airway management. Studies in spontaneously breathing patients show an almost linear relationship between flow rate and positive airway pressure in the nasopharynx. Positive airway pressure has been suggested as one of the possible mechanisms explaining how high-flow nasal therapy works. However, data on pressures generated by high-flow nasal therapy in apnoeic adults under general anaesthesia are absent. This randomised controlled crossover trial investigated airway pressures generated by different flow rates during high-flow nasal therapy in anaesthetised and paralysed apnoeic patients, comparing pressures with closed and open mouths. Following induction of anaesthesia and neuromuscular blockade, a continuous jaw thrust was used to enable airway patency. Airway pressure was measured in the right main bronchus, the middle of the trachea and the pharynx, using a fibreoptically-placed catheter connected to a pressure transducer. Each measurement was randomised with respect to closed or open mouth and different flow rates. Twenty patients undergoing elective surgery were included (mean (SD) age 38 (18) years, BMI 25.0 (3.3) kg.m-2 , nine women, ASA physical status 1 (35%), 2 (55%), 3 (10%). While closed mouths and increasing flow rates demonstrated non-linear increases in pressure, the pressure increase was negligible with an open mouth. Airway pressures remained below 10 cmH2 O even with closed mouths and flow rates up to 80 l.min-1 ; they were not influenced by catheter position. This study shows an increase in airway pressures with closed mouths that depends on flow rate. The generated pressure is negligible with an open mouth. These data question positive airway pressure as an important mechanism for maintenance of oxygenation during apnoea.

CERKL is Upregulated in Cutaneous Squamous Cell Carcinoma and Maintains Cellular Sphingolipids and Resistance to Oxidative Stress.

BACKGROUND: Ceramide Kinase-Like Protein (CERKL) was originally described in retinal tissue. CERKL has been shown to protect cells from oxidative stress, and mutations in CERKL underlie the inherited disease, retinitis pigmentosa. CERKL expression maintains cellular sphingolipids via an unknown mechanism. OBJECTIVES: To determine whether CERKL is expressed in epidermis and cutaneous squamous cell carcinoma (cSCC) and whether CERKL expression affects cSCC sphingolipid metabolism and susceptibility to oxidative stress. METHODS: CERKL expression was determined by RNA-Seq, qPCR and immunohistochemistry. CERKL was knocked down in cSCC cells using siRNA. Sphingolipid content was analyzed by liquid chromatography-mass spectrometry (LC-MS). Oxidative stress was induced by treatment with H2 O2 , and apoptosis was measured using flow cytometry to determine annexin v binding. RESULTS: CERKL mRNA and protein are highly expressed in actinic keratosis and cSCC in comparison with normal epidermis. CERKL also is expressed in metabolically active epithelial cells in normal hair bulbs and sebaceous glands. CERKL knockdown in cultured cSCC cells reduces cellular sphingolipid content and enhances susceptibility to oxidative stress. CONCLUSIONS: These findings suggest that CERKL may be important in cSCC progression and could lead to novel strategies for prevention and treatment of cSCC.

Centrally Reduced Diffusion Sign for Differentiation between Treatment-Related Lesions and Glioma Progression: A Validation Study.

BACKGROUND AND PURPOSE: Differentiating between treatment-related lesions and tumor progression remains one of the greatest dilemmas in neuro-oncology. Diffusion MR imaging characteristics may provide useful information to help make this distinction. The aim of the study was to assess the diagnostic accuracy of the centrally reduced diffusion sign for differentiation of treatment-related lesions and true tumor progression in patients with suspected glioma recurrence. MATERIALS AND METHODS: The images of 231 patients who underwent an operation for suspected glioma recurrence were reviewed. Patients with susceptibility artifacts or without central necrosis were excluded. The final diagnosis was established according to histopathology reports. Two neuroradiologists classified the diffusion patterns on preoperative MR imaging as the following: 1) reduced diffusion in the solid component only, 2) reduced diffusion mainly in the solid component, 3) no reduced diffusion, 4) reduced diffusion mainly in the central necrosis, and 5) reduced diffusion in the central necrosis only. Diagnostic accuracy metrics and the area under the receiver operating characteristic curve were estimated for the diffusion patterns. RESULTS: One hundred three patients were included (22 with treatment-related lesions and 81 with tumor progression). The diagnostic accuracy results for the centrally reduced diffusion pattern as a predictor of treatment-related lesions ("mainly central" and "exclusively central" patterns versus all other patterns) were as follows: 64% sensitivity (95% CI, 41%-83%), 84% specificity (95% CI, 74%-91%), 52% positive predictive value (95% CI, 37%-66%), and 89% negative predictive value (95% CI, 83%-94%). CONCLUSIONS: The centrally reduced diffusion sign is associated with the presence of treatment effect. The probability of a histologic diagnosis of a treatment-related lesion is low (11%) in the absence of centrally reduced diffusion.